The pharmacological efficacy of the anti-IL17 scFv and sTNFR1 bispecific fusion protein in inflammation mouse stimulated by LPS

Yang, Yuexin; Zhang, Teng; Cao, Hongxue; Yu, Dan; Zhang, Tong; Zhao, Shaojuan; Jing, Xiaohui; Song, Lun; Liu, Yunye; Che, Ruixiang; Liu, Xin; Li, Deshan; Ren, Guangxin

doi:10.1016/j.biopha.2017.05.147

Cited by 3 publications

(1 citation statement)

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“…However, almost 50% of RA patients treated with TNF-α inhibitors do not show any notable positive response; therefore, it is tempting for the researchers to speculate a fusion protein for TNF-α that participate in the proinflammatory cytokine cascade [28] and the treatment of RA. Previous studies also reported that the bispecific fusion protein has curative effectiveness for RA [23,24] or other inflammatory diseases [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Designing a new bi-specific tandem single-chain variable fragment antibody against tumor necrosis factor-α and interleukin-23 via in silico studies for the treatment of Rheumatoid arthritis

Barkhordaria

Mahnam

Sadeghi

2020

Preprint

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Background: Rheumatoid arthritis disease is a chronic autoimmune inflammatory disease that mainly causes synovial joint inflammation and cartilage destruction. Tumor necrosis factor-α (TNF-α) is a pivotal cytokine that plays an important role in rheumatoid arthritis. The treatments focusing on a single cytokine' inhibition, are able to clinically produce meaningful responses in only about half of the treated patients due to multiple cytokines involved in this disease. In the present study, a bi-specific tandem single-chain variable fragment was designed in order to suppress both human tumor necrosis factor-α and interleukin-23 (IL23) as a potential therapeutic drug candidate for this disease. To do so, at first, eight bi-specific tandem single-chain variable fragment models were built against tumor necrosis factor-α and interleukin-23 cytokines with different domain orders and then 50 ns molecular dynamics simulation was performed for each one and thereafter structural properties were exploited. Results: MD simulation results indicate that the domains' order strongly affects tandem single-chain variable fragment properties and in overall, the fragment VLIL23+Linker+VHIL23+linker+VLTNF+Linker+VHTNF +His6 (VL is variable light and VH is variable heavy fragments and His6 is six histidine) not only separated antibody domains but also had better stability and solvation energy. Conclusions: Hence, this structure can be considered as a potential drug for rheumatoid arthritis. It is hoped that this research could shed a light for the treatment of Rheumatoid arthritis disease.

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